The techniques of biochemistry and of human cell culture will be employed to explore purine and pyrimidine metabolism. The proposed investigations include a search for natural compounds that influence the velocity of pyrimidine synthesis, and a study of serum levels of certain enzymes of purine metabolism in patients with neoplastic disease. The catabolism of uracil and thymine in cultured diploid human cells will also be examined. Another project is devoted to exploring the role of natural pyrimidines and pyrimidine-like molecules in the functioning of the brain. Finally, experiments on the effect of chromosome-dosage imbalance on gene expression in human cells will be performed.